Actaea racemosa L. extract inhibits steroid sulfation in human breast cancer cells: Effects on androgen formation.
Androgens
/ metabolism
Antineoplastic Agents, Phytogenic
/ chemistry
Breast Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cimicifuga
/ chemistry
Estradiol
/ metabolism
Estrogen Receptor alpha
/ metabolism
Female
Humans
MCF-7 Cells
Plant Extracts
/ chemistry
Plant Roots
/ chemistry
Saponins
/ pharmacology
Steroids
/ metabolism
Sulfotransferases
/ metabolism
Triterpenes
/ pharmacology
Actaea racemosa L.
Actein
Breast cancer
Metabolism
SULT2A1
Steroid hormones
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
29
03
2020
revised:
26
08
2020
accepted:
24
09
2020
pubmed:
5
10
2020
medline:
17
12
2020
entrez:
4
10
2020
Statut:
ppublish
Résumé
Actaea racemosa L., also known as black cohosh, is a popular herb commonly used for the treatment of menopausal symptoms. Because of its purported estrogenic activity, black cohosh root extract (BCE) may trigger breast cancer growth. The potential effects of standardized BCE and its main constituent actein on cellular growth rates and steroid hormone metabolism were investigated in estrogen receptor alpha positive (ERα+) MCF-7 and -negative (ERα-) MDA-MB-231 human breast cancer cells. Cell numbers were determined following incubation of both cell lines with the steroid hormone precursors dehydroepiandrosterone (DHEA) and estrone (E1) for 48 h, in the presence and absence of BCE or actein. Using a validated liquid chromatography-high resolution mass spectrometry assay, cell culture supernatants were simultaneously analyzed for the ten main steroids of the estrogen pathway. Inhibition of MCF-7 and MDA-MB-231 cell growth (up to 36.9%) was observed following treatment with BCE (1-25 µg/ml) or actein (1-50 µM). Incubation of MCF-7, but not of MDA-MB-231 cells, with DHEA and BCE caused a 20.9% reduction in DHEA-3-O-sulfate (DHEA-S) formation, leading to a concomitant increase in the androgens 4-androstene-3,17-dione (AD) and testosterone (T). Actein was shown to exert an even stronger inhibitory effect on DHEA-S formation in MCF-7 cells (up to 89.6%) and consequently resulted in 12- to 15-fold higher androgen levels compared with BCE. The formation of 17β-estradiol (E2) and its glucuronidated and sulfated metabolites was not affected by BCE or actein after incubation with the estrogen precursor estrone (E1) in either cell line. The results of the present study demonstrated that actein and BCE do not promote breast cancer cell growth or influence estrogen levels. However, androgen formation was strongly stimulated by BCE and actein, which may contribute to their ameliorating effects on menopausal symptoms in women. Future studies monitoring the levels of AD and T upon BCE supplementation of patients are warranted to verify an association between BCE and endogenous androgen metabolism.
Sections du résumé
BACKGROUND
BACKGROUND
Actaea racemosa L., also known as black cohosh, is a popular herb commonly used for the treatment of menopausal symptoms. Because of its purported estrogenic activity, black cohosh root extract (BCE) may trigger breast cancer growth.
STUDY DESIGN/METHODS
METHODS
The potential effects of standardized BCE and its main constituent actein on cellular growth rates and steroid hormone metabolism were investigated in estrogen receptor alpha positive (ERα+) MCF-7 and -negative (ERα-) MDA-MB-231 human breast cancer cells. Cell numbers were determined following incubation of both cell lines with the steroid hormone precursors dehydroepiandrosterone (DHEA) and estrone (E1) for 48 h, in the presence and absence of BCE or actein. Using a validated liquid chromatography-high resolution mass spectrometry assay, cell culture supernatants were simultaneously analyzed for the ten main steroids of the estrogen pathway.
RESULTS
RESULTS
Inhibition of MCF-7 and MDA-MB-231 cell growth (up to 36.9%) was observed following treatment with BCE (1-25 µg/ml) or actein (1-50 µM). Incubation of MCF-7, but not of MDA-MB-231 cells, with DHEA and BCE caused a 20.9% reduction in DHEA-3-O-sulfate (DHEA-S) formation, leading to a concomitant increase in the androgens 4-androstene-3,17-dione (AD) and testosterone (T). Actein was shown to exert an even stronger inhibitory effect on DHEA-S formation in MCF-7 cells (up to 89.6%) and consequently resulted in 12- to 15-fold higher androgen levels compared with BCE. The formation of 17β-estradiol (E2) and its glucuronidated and sulfated metabolites was not affected by BCE or actein after incubation with the estrogen precursor estrone (E1) in either cell line.
CONCLUSIONS
CONCLUSIONS
The results of the present study demonstrated that actein and BCE do not promote breast cancer cell growth or influence estrogen levels. However, androgen formation was strongly stimulated by BCE and actein, which may contribute to their ameliorating effects on menopausal symptoms in women. Future studies monitoring the levels of AD and T upon BCE supplementation of patients are warranted to verify an association between BCE and endogenous androgen metabolism.
Identifiants
pubmed: 33011631
pii: S0944-7113(20)30188-4
doi: 10.1016/j.phymed.2020.153357
pii:
doi:
Substances chimiques
Androgens
0
Antineoplastic Agents, Phytogenic
0
ESR1 protein, human
0
Estrogen Receptor alpha
0
Plant Extracts
0
Saponins
0
Steroids
0
Triterpenes
0
Estradiol
4TI98Z838E
Sulfotransferases
EC 2.8.2.-
alcohol sulfotransferase
EC 2.8.2.2
actein
I14QO4LW9V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153357Subventions
Organisme : Austrian Science Fund FWF
ID : I 3417
Pays : Austria
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.